This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Noroviruses, including Norwalk, are non-cultivatable human Caliciviruses that have emerged as the single most significant cause of epidemic outbreaks of nonbacterial gastroenteritis, which is an acute debilitating illness characterized by a fever, headache, vomiting and diarrhea. According to CDC estimates, 23 million cases of acute gastroenteritis are due to Norovirus each year in the U.S. alone placing a significant socioeconomic toll on businesses, hospitals, schools and other closed settings dealing with outbreaks. These viruses are also the most common cause of outbreaks of nonbacterial gastroenteritis worldwide, where acute viral gastroenteritis is a leading cause of infant mortality. The new vaccine to be studied in this protocol is based on Norwalk Virus-Like-Particles (VLP) as the immunogen. Norwalk VLPs are non-infectious because they do not contain viral genomic RNA, and they are highly immunogenic because they preserve particulate antigen confirmation and structure to mimic functional interactions of the virus with cellular receptors, thereby eliciting a strong host immune response.